Cryptogenic strokes and transient ischemic attacks (“TIAs”) are those in which no obvious cause is found by patient history, carotid Doppler studies, or cardiac conditions such as atrial fibrillation, myocardial infarction, or valve diseases. Patent foramen ovale (“PFO”), which is a small flap-valve hole in the heart, has been associated with cryptogenic stroke allowing paradoxical embolism from the veins to the brain through a right-to-left shunt (“RLS”). Normally, blood returning to the heart from the veins is re-oxygenated when it is pumped from the right side of the heart and then through the lungs. However, in people with PFO, the venous blood, which may contain clots, may instead travel through the hole (i.e., the PFO) between the upper chambers of the heart and into the arterial blood, bypassing the lungs where the clots would normally be filtered out. When this blood goes to the brain, a clot may cause a stroke or stroke-like symptoms. In approximately 40 percent of stroke cases, the underlying cause is difficult to determine and the stroke is called “cryptogenic”. Evidence now suggests that when a person has a stroke, and its cause is undetermined, the person is about twice as likely as the normal population to have PFO.
Currently, PFO is considered when stroke occurs in young people. However, PFO is found in all ages; 34% of adults in the first three decades of life declining to 20% in the 9th and 10th decades and ranging from 1 to 19 mm in diameter. Cryptogenic stroke patients, assessed with traditional single gate transcranial Doppler (“sgTCD”), have 12 to 1 odds of having a large PFO compared to a non-stroke group. Also, migraine patients with aura have a 3 to 1 odds of having a PFO compared to a non-migraine group. Conditions for venous thrombosis and pulmonary embolism also exist widely and deep vein thrombosis is a common finding in the vascular laboratory. Therefore, the conditions for paradoxical embolism are widely prevalent at all ages.
Atrial septal defect (“ASD”) is a permanent opening through the interatrial septum that often persists into adulthood. Blood flows back and forth through the defect depending on the back and forth pressure gradient between the atria. This defect usually places a load on the right ventricle that, however, may be tolerated for many years. If the mean right atrial pressure is chronically elevated these patients have a significant desaturation of the arterial blood.
The urgency to diagnose PFO and ASD is driven by the advent of safe transcatheter closure devices and the popularity of TCD over invasive transesophageal echocardiography (“TEE”) has enhanced the search for PFO and ASD. sgTCD has demonstrated high accuracy in ruling in, and ruling out, PFO when compared to TEE. Particularly, sgTCD is able to detect large shunts, which are more clinically relevant. Using intravenous injections of agitated saline, which provide an ultrasonic contrast agent of bubbles, the suspended bubbles pass through the PFO from the right to the left atrium and are easily detected by TCD as audible chirps and microembolic spectra in the cerebral arteries. Agitated saline contrast agent has been used safely for many years in echocardiography and TCD. As known, bubbles in agitated saline do not pass the lungs, and therefore a shunt from the venous system to the arterial system which bypasses the lungs is the only way for bubbles to be seen on the arterial side. A Valsalva strain (forced expiratory effort against a closed glottis) facilitates passage of the microbubbles through the PFO by raising the pressure in the right atrium over that of the left atrium.
TEE is currently considered the “gold standard” for PFO diagnosis. However, it is poorly tolerated by patients and requires deep sedation, which limits the patient's ability to perform a Valsalva maneuver. sgTCD has proven to be a reliable technique for diagnosing PFO. While PFO diagnosis and treatment are facilitated by TCD's less invasive technology, sgTCD and TEE are limited by a grading system that uses 3 categories to rate the degree of RLS. In patients with ischemic or cryptogenic stroke, the need exists to further quantify RLS.
An improvement over the use of TEE and sgTCD for evaluating PFO is provided by recently developed multi-gate power m-mode TCD (pmTCD) ultrasound devices. An example of such an ultrasound system is the digital Doppler platform developed by Spencer Technologies in Seattle, Wash. in which up to 33 sample gates placed at 2 mm intervals can be simultaneously processed into a “color” power m-mode image. The color in the m-mode image is a function of Doppler signature power and detected velocity, in that increases in backscattered power cause the colors, red or blue, to become more intense. Additionally, a spectrogram for a selected depth in the depth range can be displayed. The digital Doppler platform is referred to as Spencer Technologies' Power M-mode Doppler (“PMD”). Showing power in this fashion conveys to the user when the Doppler beam is well aimed—that is, intensity of color increases with volume of moving blood in the Doppler sample volume and this indicates when the beam is centered on the blood flow. Thus, the color m-mode display of an ultrasound system having PMD capability provides medical professionals who do not have expertise in ultrasound with a mechanism for easy location (by the operator) of the middle cerebral circulation. A more detailed description of PMD ultrasound systems can be found in U.S. Pat. No. 6,196,972 to Moehring, issued Mar. 6, 2001 and assigned to Spencer Technologies.
In an application evaluating PFO, pmTCD detects 66% more bubble microemboli than traditional sgTCD. The increased detectability allows for use of an expanded six-level grading scale to rate the degree of RLS, in contrast to the three-level grading system provided by TEE and sgTCD. In performing the evaluation of PFO using pmTCD, bilateral monitoring is performed with the beam including the ipsilateral middle cerebral and anterior cerebral arteries (“MCAs”) and (“ACAs”). The two probes are positioned bilaterally and stabilized using a head-frame worn by the patient. The spectrogram sample volumes of the PMD are set near the origin of each respective MCA at a depth of 50 mm to 60 mm. The PMD is observed for embolic tracks (“ETs”) while listening to the MCA spectral signal.
In observing the bubble emboli, pmTCD produces unique signatures of emboli, appearing as brightly colored ETs as they pass through the insonated arteries. When an embolus moves toward the transducer, a bright red upward-sloping ET is produced. In contrast, when an embolus moves away from the transducer, a bright blue downward-sloping ET is produced. The sloping feature of the ET is prima facie evidence of an embolus (i.e., a bubble or particle) carried by the blood through a vessel within the ultrasound beam. The slope shows the embolus velocity as a change in depth over time. If the single gate is placed in any of the colored bands, ETs also appear on the spectrogram as high intensity microembolic signals (“MESs”).
For PFO evaluation, generally, all ETs are counted in the bilaterally insonated arteries from a depth range of approximately 40 mm to 75 mm. Typically, all ETs and MESs are counted visually. Because the beams overlap at the midline at a depth of 75 mm, ETs are not counted at depths beyond 75 mm. Based on the number of ETs counted, a grade is determined according to following the expanded six-level logarithmic grading scale to rate the degree of RLS: grade 0=0 ETs, grade I=1-10 ETs, grade II=11-30 ETs, grade III=31-100 ETs, grade IV=101-300 ETs, and grade V>300 ETs. The expanded six-level grading scale does not predict the size of the opening, but does provide a measure of the conductance or ability of the opening to transmit material from the venous circulation to the brain. That is, the numbers of ETs represent tracers of the conductance of RLS flow to the anterior circulation of the brain. The conductance takes into account many factors including the RLS flow distribution to the anterior circulation of the brain, the size of the foramen while open, and the right-to-left pressure gradient when the foramen is open. For unilateral pmTCD monitoring, the number of ETs counted are doubled and the resulting number applied to the six-level grading scale accordingly.
The use of pmTCD has provided greater accuracy and an improved grading scale for determining the functional conductance of PFO. However, the process of visually counting the ETs detected during examination can be time consuming. Thus, immediate grading of PFO for the higher grades is unlikely. Additionally, counting the number of ETs for the higher grades, such as grades 4 and above, is often difficult as visually distinguishing between individual ETs on a PMD monitor for higher grades, that is, those grades having higher number and density of ETs, may not be possible. As a result, the grading process, specifically for PFO, and more generally, for any visual counting or grading process based on the number of ETs, is susceptible to counting errors. Moreover, due to the practical limitations of visually counting individual ETs at higher densities of ETs, further expansion of a grading scale to provide greater grading resolution may not be possible.